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Discovery of Clinical Candidate 1-{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent, Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by Fragment-Based Drug Design.
Lee KL, Ambler CM, Anderson DR, Boscoe BP, Bree AG, Brodfuehrer JI, Chang JS, Choi C, Chung S, Curran KJ, Day JE, Dehnhardt CM, Dower K, Drozda SE, Frisbie RK, Gavrin LK, Goldberg JA, Han S, Hegen M, Hepworth D, Hope HR, Kamtekar S, Kilty IC, Lee A, Lin LL, Lovering FE, Lowe MD, Mathias JP, Morgan HM, Murphy EA, Papaioannou N, Patny A, Pierce BS, Rao VR, Saiah E, Samardjiev IJ, Samas BM, Shen MWH, Shin JH, Soutter HH, Strohbach JW, Symanowicz PT, Thomason JR, Trzupek JD, Vargas R, Vincent F, Yan J, Zapf CW, Wright SW. Lee KL, et al. Among authors: dower k. J Med Chem. 2017 Jul 13;60(13):5521-5542. doi: 10.1021/acs.jmedchem.7b00231. Epub 2017 Jun 14. J Med Chem. 2017. PMID: 28498658
The Interleukin-1 Receptor-Associated Kinase 4 Inhibitor PF-06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial.
Winkler A, Sun W, De S, Jiao A, Sharif MN, Symanowicz PT, Athale S, Shin JH, Wang J, Jacobson BA, Ramsey SJ, Dower K, Andreyeva T, Liu H, Hegen M, Homer BL, Brodfuehrer J, Tilley M, Gilbert SA, Danto SI, Beebe JJ, Barnes BJ, Pascual V, Lin LL, Kilty I, Fleming M, Rao VR. Winkler A, et al. Among authors: dower k. Arthritis Rheumatol. 2021 Dec;73(12):2206-2218. doi: 10.1002/art.41953. Epub 2021 Nov 1. Arthritis Rheumatol. 2021. PMID: 34423919 Free PMC article. Clinical Trial.
Discovery of PF-06928215 as a high affinity inhibitor of cGAS enabled by a novel fluorescence polarization assay.
Hall J, Brault A, Vincent F, Weng S, Wang H, Dumlao D, Aulabaugh A, Aivazian D, Castro D, Chen M, Culp J, Dower K, Gardner J, Hawrylik S, Golenbock D, Hepworth D, Horn M, Jones L, Jones P, Latz E, Li J, Lin LL, Lin W, Lin D, Lovering F, Niljanskul N, Nistler R, Pierce B, Plotnikova O, Schmitt D, Shanker S, Smith J, Snyder W, Subashi T, Trujillo J, Tyminski E, Wang G, Wong J, Lefker B, Dakin L, Leach K. Hall J, et al. Among authors: dower k. PLoS One. 2017 Sep 21;12(9):e0184843. doi: 10.1371/journal.pone.0184843. eCollection 2017. PLoS One. 2017. PMID: 28934246 Free PMC article.
Interleukin 1/Toll-like receptor-induced autophosphorylation activates interleukin 1 receptor-associated kinase 4 and controls cytokine induction in a cell type-specific manner.
Cushing L, Stochaj W, Siegel M, Czerwinski R, Dower K, Wright Q, Hirschfield M, Casanova JL, Picard C, Puel A, Lin LL, Rao VR. Cushing L, et al. Among authors: dower k. J Biol Chem. 2014 Apr 11;289(15):10865-10875. doi: 10.1074/jbc.M113.544809. Epub 2014 Feb 24. J Biol Chem. 2014. PMID: 24567333 Free PMC article.
Efficacy and Pharmacology of the NLRP3 Inflammasome Inhibitor CP-456,773 (CRID3) in Murine Models of Dermal and Pulmonary Inflammation.
Primiano MJ, Lefker BA, Bowman MR, Bree AG, Hubeau C, Bonin PD, Mangan M, Dower K, Monks BG, Cushing L, Wang S, Guzova J, Jiao A, Lin LL, Latz E, Hepworth D, Hall JP. Primiano MJ, et al. Among authors: dower k. J Immunol. 2016 Sep 15;197(6):2421-33. doi: 10.4049/jimmunol.1600035. Epub 2016 Aug 12. J Immunol. 2016. PMID: 27521339
TREM-1 expression is increased in the synovium of rheumatoid arthritis patients and induces the expression of pro-inflammatory cytokines.
Kuai J, Gregory B, Hill A, Pittman DD, Feldman JL, Brown T, Carito B, O'Toole M, Ramsey R, Adolfsson O, Shields KM, Dower K, Hall JP, Kurdi Y, Beech JT, Nanchahal J, Feldmann M, Foxwell BM, Brennan FM, Winkler DG, Lin LL. Kuai J, et al. Among authors: dower k. Rheumatology (Oxford). 2009 Nov;48(11):1352-8. doi: 10.1093/rheumatology/kep235. Epub 2009 Aug 27. Rheumatology (Oxford). 2009. PMID: 19713442
35 results